Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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Unveiling the link between arsenic toxicity and diabetes: an in silico exploration into the role of transcription factors

  • Kaniz Fatema (Department of Genetic Engineering & Biotechnology, University of Dhaka) ;
  • Zinia Haidar (Department of Genetic Engineering & Biotechnology, University of Dhaka) ;
  • Md Tamzid Hossain Tanim (Department of Genetic Engineering & Biotechnology, University of Dhaka) ;
  • Sudipta Deb Nath (Department of Genetic Engineering & Biotechnology, University of Dhaka) ;
  • Abu Ashfaqur Sajib (Department of Genetic Engineering & Biotechnology, University of Dhaka)
  • Received : 2023.10.18
  • Accepted : 2024.07.10
  • Published : 2024.10.15
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Abstract

Arsenic-induced diabetes, despite being a relatively newer finding, is now a growing area of interest, owing to its multifaceted nature of development and the diversity of metabolic conditions that result from it, on top of the already complicated manifestation of arsenic toxicity. Identification and characterization of the common and differentially affected cellular metabolic pathways and their regulatory components among various arsenic and diabetes-associated complications may aid in understanding the core molecular mechanism of arsenic-induced diabetes. This study, therefore, explores the effects of arsenic on human cell lines through 14 transcriptomic datasets containing 160 individual samples using in silico tools to take a systematic, deeper look into the pathways and genes that are being altered. Among these, we especially focused on the role of transcription factors due to their diverse and multifaceted roles in biological processes, aiming to comprehensively investigate the underlying mechanism of arsenic-induced diabetes as well as associated health risks. We present a potential mechanism heavily implying the involvement of the TGF-β/SMAD3 signaling pathway leading to cell cycle alterations and the NF-κB/TNF-α, MAPK, and Ca2+ signaling pathways underlying the pathogenesis of arsenic-induced diabetes. This study also presents novel findings by suggesting potential associations of four transcription factors (NCOA3, PHF20, TFDP1, and TFDP2) with both arsenic toxicity and diabetes; five transcription factors (E2F5, ETS2, EGR1, JDP2, and TFE3) with arsenic toxicity; and one transcription factor (GATA2) with diabetes. The novel association of the transcription factors and proposed mechanism in this study may serve as a take-of point for more experimental evidence needed to understand the in vivo cellular-level diabetogenic effects of arsenic.

Keywords

Acknowledgement

This study was supported by a Grant on Advanced Research in Education (GARE) from the Ministry of Education, Bangladesh. The authors are thankful for the support.

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